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  • Open Access

    ARTICLE

    Substrate Modulation of Osteoblast Adhesion Strength, Focal Adhesion Kinase Activation, and Responsiveness to Mechanical Stimuli

    E. Takai1, R. Landesberg2, R.W. Katz2, C.T. Hung3, X.E Guo1,4

    Molecular & Cellular Biomechanics, Vol.3, No.1, pp. 1-12, 2006, DOI:10.3970/mcb.2006.003.001

    Abstract Osteoblast interactions with extracellular matrix (ECM) proteins are known to influence many cell functions, which may ultimately affect osseointegration of implants with the host bone tissue. Some adhesion-mediated events include activation of focal adhesion kinase, and subsequent changes in the cytoskeleton and cell morphology, which may lead to changes in adhesion strength and cell responsiveness to mechanical stimuli. In this study we examined focal adhesion kinase activation (FAK), F-actin cytoskeleton reorganization, adhesion strength, and osteoblast responsiveness to fluid shear when adhered to type I collagen (ColI), glass, poly-L-lysine (PLL), fibronectin (FN), vitronectin (VN), and serum (FBS). In general, surfaces that… More >

  • Open Access

    ARTICLE

    Systolic Modeling of the Left Ventricle as a Mechatronic System: Determination of Myocardial Fiber's Sarcomere Contractile Characteristics and New Performance Indices

    Dhanjoo N. Ghista1,2, Liang Zhong2, Leok P.Chua2, Eddie Y-K Ng2, Soo T.Lim3, Ru S. Tan3, TerranceS-J Chua3

    Molecular & Cellular Biomechanics, Vol.2, No.4, pp. 217-234, 2005, DOI:10.3970/mcb.2005.002.217

    Abstract Background: In this paper, the left ventricle (LV) is modeled as a cylinder with myocardial fibers located helically within its wall. A fiber is modeled into myocardial structural units (MSUs); the core entity of each MSU is the sarcomeric contractile element. The relationship between the sarcomere unit's contractile force and shortening velocity is expressed in terms of the LV model's wall stress and deformation, and hence in terms of the monitored LV pressure and volume. Then, the LV systolic performance is investigated in terms of a mechatronic (excitation-contraction) model of the sarcomere unit located within the LV cylindrical model wall.… More >

  • Open Access

    ARTICLE

    Intracellular stress transmission through actin stress fiber network in adherent vascular cells

    S. Deguchi1,2, T. Ohashi2, M. Sato2

    Molecular & Cellular Biomechanics, Vol.2, No.4, pp. 205-216, 2005, DOI:10.3970/mcb.2005.002.205

    Abstract Intracellular stress transmission through subcellular structural components has been proposed to affect activation of localized mechano-sensing sites such as focal adhesions in adherent cells. Previous studies reported that physiological extracellular forces produced heterogeneous spatial distributions of cytoplasmic strain. However, mechanical signaling pathway involved in intracellular force transmission through basal actin stress fibers (SFs), a mechano-responsive cytoskeletal structure, remains elusive. In the present study, we investigated force balance within the basal SFs of cultured smooth muscle cells and endothelial cells by (i) removing the cell membrane and cytoplasmic constituents except for materials physically attaching to the substrate (i.e., SF--focal adhesion complexities)… More >

  • Open Access

    ARTICLE

    The Effect of Matrix Tension-Compression Nonlinearity and Fixed Negative Charges on Chondrocyte Responses in Cartilage

    Morakot Likhitpanichkul1, X. Edward Guo2, Van C. Mow1,3

    Molecular & Cellular Biomechanics, Vol.2, No.4, pp. 191-204, 2005, DOI:10.3970/mcb.2005.002.191

    Abstract Thorough analyses of the mechano-electrochemical interaction between articular cartilage matrix and the chondrocytes are crucial to understanding of the signal transduction mechanisms that modulate the cell metabolic activities and biosynthesis. Attempts have been made to model the chondrocytes embedded in the collagen-proteoglycan extracellular matrix to determine the distribution of local stress-strain field, fluid pressure and the time-dependent deformation of the cell. To date, these models still have not taken into account a remarkable characteristic of the cartilage extracellular matrix given rise from organization of the collagen fiber architecture, now known as the tension-compression nonlinearity (TCN) of the tissue, as well… More >

  • Open Access

    ARTICLE

    Misfolding Dynamics of Human Prion Protein

    Muhammad H. Zaman1

    Molecular & Cellular Biomechanics, Vol.2, No.4, pp. 179-190, 2005, DOI:10.3970/mcb.2005.002.179

    Abstract We report the results of longest to date simulation on misfolding of monomeric human prion protein (HuPrP). By comparing our simulation of a partially unfolded protein to the simulation of the native protein, we observe that the native protein as well as native regions in the partially unfolded protein remain in the native state, and the unfolded regions fold back with increased extended (sheet and PP-II) conformations. The misfolded regions show increased basin hopping from non-helical basins while the amino acids locked in the helical conformation tend to stay locked in that conformation. Our results also validate the hypothesis that… More >

  • Open Access

    ARTICLE

    Forced Dissociation of Selectin-ligand Complexes Using Steered Molecular Dynamics Simulation

    Shouqin Lü1, Mian Long1,2

    Molecular & Cellular Biomechanics, Vol.2, No.4, pp. 161-178, 2005, DOI:10.3970/mcb.2005.002.161

    Abstract Selectin-ligand interactions are crucial to such biological processes as inflammatory cascade or tumor metastasis. How transient formation and dissociation of selectin-ligand bonds in blood flow are coupled to molecular conformation at atomic level, however, has not been well understood. In this study, steered molecular dynamics (SMD) simulations were used to elucidate the intramolecular and intermolecular conformational evolutions involved in forced dissociation of three selectin-ligand systems: the construct consisting of P-selectin lectin (Lec) and epidermal growth factor (EGF)-like domains (P-LE) interacting with synthesized sulfoglycopeptide or SGP-3, P-LE with sialyl Lewis X (sLeX), and E-LE with sLeX. SMD simulations were based on… More >

  • Open Access

    ARTICLE

    Melanoma Cell Extravasation under Flow Conditions Is Modulated by Leukocytes and Endogenously Produced Interleukin 8

    Cheng Dong1,2,3, Margaret J. Slattery2,3, Shile Liang3, Hsin-Hsin Peng2

    Molecular & Cellular Biomechanics, Vol.2, No.3, pp. 145-160, 2005, DOI:10.3970/mcb.2005.002.145

    Abstract Attachment of tumor cells to the endothelium (EC) under flow conditions is critical for the migration of tumor cells out of the vascular system to establish metastases. Innate immune system processes can potentially promote tumor progression through inflammation dependant mechanisms.\nobreakspace {} White blood cells, neutrophils (PMN) in particular, are being studied to better understand how the host immune system affects cancer cell adhesion and subsequent migration and metastasis. Melanoma cell interaction with the EC is distinct from PMN-EC adhesion in the circulation. We found PMN increased melanoma cell extravasation, which involved initial PMN tethering on the EC, subsequent PMN capture… More >

  • Open Access

    ARTICLE

    Control of the Direction of Lamellipodia Extension through Changes in the Balance between Rac and Rho Activities

    A.L. Brock, D.E. Ingber1

    Molecular & Cellular Biomechanics, Vol.2, No.3, pp. 135-144, 2005, DOI:10.3970/mcb.2005.002.135

    Abstract The direction in which cells extend new motile processes, such as lamellipodia and filopodia, can be controlled by altering the geometry of extracellular matrix adhesive islands on which individual cells are cultured, thereby altering mechanical interactions between cells and the adhesive substrate [Parker (2002)]. Here we specifically investigate the intracellular molecular signals that mediate the mechanism by which cells selectively extend these processes from the corners of polygonal-shaped adhesive islands. Constitutive activation of the small GTPase Rac within cells cultured on square-shaped islands of fibronectin resulted in the elimination of preferential extension from corners. This loss of directionality was accompanied… More >

  • Open Access

    ARTICLE

    Evaluation of Tension in Actin Bundle of Endothelial Cells Based on Preexisting Strain and Tensile Properties Measurements

    S. Deguchi1,2, T. Ohashi2, M. Sato2

    Molecular & Cellular Biomechanics, Vol.2, No.3, pp. 125-134, 2005, DOI:10.3970/mcb.2005.002.125

    Abstract Actin bundles in vascular endothelial cells (ECs) play a critical role in transmitting intracellular forces between separate focal adhesion sites. However, quantitative descriptions of tension level in single actin bundles in a physiological condition are still poorly studied. Here, we evaluated magnitude of preexisting tension in a single actin bundle of ECs on the basis of measurements of its preexisting stretching strain and tensile properties. Cultured ECs expressing fluorescently-labeled actin were treated with detergents to extract acin bundles. One end of an actin bundle was then dislodged from the substrate by using a microneedle, resulting in a shortening of the… More >

  • Open Access

    REVIEW

    Biophysical approaches for studying the integrity and function of tight junctions

    S.R.K. Vedula1, T.S. Lim2, P.J. Kausalya3, W. Hunziker3, G. Rajagopal2, C.T. Lim1,4

    Molecular & Cellular Biomechanics, Vol.2, No.3, pp. 105-124, 2005, DOI:10.3970/mcb.2005.002.105

    Abstract Cell-cell adhesion is an extremely important phenomenon as it influences several biologically important processes such as inflammation, cell migration, proliferation, differentiation and even cancer metastasis. Furthermore, proteins involved in cell-cell adhesion are also important from the perspective of facilitating better drug delivery across epithelia. The adhesion forces imparted by proteins involved in cell-cell adhesion have been the focus of research for sometime. However, with the advent of nanotechnological techniques such as the atomic force microscopy (AFM), we can now quantitatively probe these adhesion forces not only at the cellular but also molecular level. Here, we review the structure and function… More >

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